Research by members of the Cell Growth and Differentiation Control Program is focused on identifying and understanding the mechanisms of action of the cellular factors that control proliferation, differentiation and cell death, how the programs controlling these processes are coordinated and how they interact. The major scientific goals are: (1) to identify, characterize and study the mechanisms of action of gene products controlling cell proliferation, lineage commitment and cell differentiation, and cell death; (2) to understand how misregulation of these gene products and processes contribute to oncogenesis; (3) to use this knowledge to develop new approaches to cancer prevention and treatment. A major scientific focus of the program is the control of gene expression during the cell cycle, differentiation and apoptosis and the key role played by transcription factors in regulating these processes. Many members of the program are also studying the role of epigenetic mechanisms in cancer, including changes in the patterns of histone modifications and DMA methylation in cancer cells. A new method for genome-wide methylation analyses has been developed by a program member for these studies and, along with a highly versatile array platform, is being used to study gene expression and epigenetic changes during normal cell growth and differentiation in a variety of malignancies and premalignant conditions. Within the program there are particular strengths in studying the properties of stem cells, both adult stem cells and human embryonic stem cells, as well as in three organ systems: the hematopoietic system, the liver, and neuronal cells. The program has benefited from members whose research programs utilize nonmammalian model organisms including yeast, Drosophila, and zebrafish. The research of the group's members is also strengthened by investigators with expertise in the most advanced approaches for studying control of gene expression in eukaryotic cells. There are currently 26 program members from 10 departments, of whom 25 are primary members, supported by 9 NCI ($1.8M Direct) and 33 other NIH grants. There have been 5 new recruits to this program. Since the last CCSG review there have been 439 cancer-relevant research papers by members of this program of which 8% represent intraprogrammatic, and 20% represent interprogrammatic collaborations.